In the past year, we have begun work in two new areas: (1) Optical pumping of NMR signals. We are exploring the possibility of greatly enhancing the sensitivity of NMR measurements, with the goal of enabling structural studies of peptides and proteins in sub-nanomole quantities, by optical excitation of large, nonequilibrium nuclear spin polarizations. Our current strategy is to optically pump nuclear spin polarization in an inorganic semiconductor crystal, then transfer the spin polarization to biological material deposited on the semiconductor surface. We have demonstrated that the spin polarization of phosphorus-31 nuclei in the semiconductor indium phosphide can be enhanced by a factor of 1500 by optical pumping with near-infrared laser light. We have also demonstrated that nuclear spin polarization can be transferred between phosphorus-31 nuclei in indium phosphide crystallites and hydrogen nuclei in organic compounds adsorbed on the crystallite surfaces. Prospects for significant sensitivity enhancement by optical pumping therefore look good. (2) Solid state NMR methodology for global structural studies of uniformly labeled proteins. Structural studies of proteins and peptides by solid state NMR are currently limited to the determination of local structural features, such as specific interatomic distances and torsional angles, in selectively isotopically labeled samples. Methods for determining global folds of uniformly isotopically labeled proteins would greatly expand the impact of solid state NMR. Such methods do not currently exist because of difficulties in resolving and assigning NMR signals from uniformly labeled proteins, low sensitivity, and hardware limitations. We are developing a new approach to this problem based on high-field, directly-detected carbon-13 NMR measurements on oriented proteins. Experiments on model peptides show that the orientation-dependent chemical shifts, carbon-carbon dipole couplings, and carbon-nitrogen dipole couplings of backbone carbonyl carbons can be independently measured in simple multidimensional NMR spectra obtained in a 17.6 Tesla field (750 MHz spectrometer). Measurement of these parameters for each residue in a protein, together with a small number of interresidue distances, should permit the determination of a complete structure.